Back to resultsMaternal/Infant Peripartum NVP, Versus Infant Only Peripartum NVP, or Maternal LPV/r in Addition to Standard ZDV Prophylaxis for the Prevention of Perinatal (PMTCT) HIV in Thailand (PHPT-5)
Primary Purpose
HIV Infections, Pregnancy
Status
Terminated
Phase
Phase 3
Locations
Thailand
Study Type
Interventional
Intervention
Maternal and infant nevirapine
Maternal placebo and infant nevirapine
Maternal lopinavir+ritonavir
zidovudine
Sponsored by
About this trial
This is an interventional prevention trial for HIV Infections focused on measuring Thailand, Developing Countries, Prophylaxis, Mother-to-child transmission, HIV-1, HIV-1 infection, HIV Seronegativity
Eligibility Criteria
Pre-Entry Criteria
- Evidence of HIV infection (documented by two HIV antibody tests on two different dates)
- Intend to be followed at a study site for the duration of the study
- At least 18 years old
- Written informed consent.
Inclusion Criteria:
Women are eligible for the study if they
- met all pre-entry criteria
- Evidence of HIV infection, as documented by two serology tests obtained at two different dates;
- between 28 and 36 weeks gestational age;
- antiretroviral naïve except for exposure to ZDV prophylaxis PMTCT;
- CD4 count above 250 cells/mm3 (within 4 months prior to randomization)
- agreement not to breastfeed;
- consent to participate and to be followed for the duration of the study;
- and the following laboratory values within 14 days prior to randomization:
- hemoglobin > 8.5 mg/dl;
- absolute neutrophil count > 750 cells/mm3;
- platelets > 50,000 cells/mm3;
- SGPT ≤ 5 times upper limit of normal;
- serum creatinine ≤ 1.5 times upper limit of normal (women with a serum creatinine > 1.5 times upper limit of normal must have a measured eight-hour urine creatinine clearance > 70 ml/min).
Exclusion criteria:
- Evidence of pre-existing fetal anomalies incompatible with life;
- patients who meet the criteria of Classes III/IV of the WHO classification of HIV-associated clinical disease;
- known hypersensitivity to any benzodiazepine;
- active tuberculosis;
- concurrent participation to any other clinical trial;
- receipt of benzodiazepines or antiretroviral agent other than ZDV;
- uncontrolled hypertension;
- anticoagulant therapy or magnesium sulfate within 2 weeks of enrollment or the need for them during labor or at delivery.
If any of these conditions occurs after randomization, the women will be excluded from study drug dosing. Women with CD4 count lower than 250 cells/mm3 will be excluded from the study and offered HAART in the context of the national program.
Sites / Locations
- Nopparat Rajathanee Hospital
- Bhumibol Adulyadej Hospital
- Chachoengsao Hospital
- Prapokklao Hospital
- Nakornping Hospital
- Sanpatong Hospital
- Mae Chan Hospital
- Mae Sai Hospital
- Phan Hospital
- Chiang Saen Hospital
- Chiangrai Prachanukroh Hospital
- Wiangpapao Hospital
- Banglamung Hospital
- Chonburi Hospital
- Panasnikom Hospital
- Ao Udom Hospital
- Kalasin Hospital
- Phaholpolphayuhasena Hospital
- Khon Kaen Hospital
- Lampang Hospital
- Mahasarakam Hospital
- Maharaj Nakhon Si Thammarat Hospital
- Nakhonpathom Hospital
- Nong Khai Hospital
- Pranangklao Hospital
- Pathumthani Hospital
- Chiang Kham Hospital
- Buddhachinaraj Hospital
- Rayong Hospital
- Samutsakhon Hospital
- Songkhla Hospital
- Hat Yai Hospital
- Trat Hospital
- Health Promotion Hospital Regional Center I
- Health Promotion Center Region 10,
- Fang Hospital
- Chomthong Hospital
- Somdej Pranangchao Sirikit Hospital
- Regional Health Promotion Centre 6,
- Lamphun Hospital
- Phayao Provincial Hospital
- Vachira Phuket Hospital
- Samutprakarn Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
1
2
3
Arm Description
NVP-NVP: In women, one NVP 200 mg tablet at onset of labor; In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
PL-NVP: In women, one placebo tablet at onset of labor; In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
LPV/r: In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
Outcomes
Primary Outcome Measures
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Secondary Outcome Measures
Safety for mothers and children of two NVP doses in neonates with and without maternal single dose NVP at onset of labor or LPV/r from 28 weeks gestation.
Full Information
NCT ID
NCT00409591
First Posted
December 8, 2006
Last Updated
January 26, 2016
Sponsor
Institut de Recherche pour le Developpement
Collaborators
Harvard School of Public Health (HSPH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT00409591
Brief Title
Maternal/Infant Peripartum NVP, Versus Infant Only Peripartum NVP, or Maternal LPV/r in Addition to Standard ZDV Prophylaxis for the Prevention of Perinatal (PMTCT) HIV in Thailand
Acronym
PHPT-5
Official Title
Maternal and Infant Peripartum Nevirapine, Versus Infant Only Peripartum Nevirapine, or Maternal Lopinavir/Ritonavir in Addition to Standard Zidovudine Prophylaxis for the Prevention of Perinatal HIV in Thailand.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Terminated
Why Stopped
Change in National PMTCT guidelines in Thailand
Study Start Date
July 2008 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherche pour le Developpement
Collaborators
Harvard School of Public Health (HSPH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare the efficacy of two doses of nevirapine (NVP) given only to the infants or lopinavir/ritonavir (LPV/r) from 28 weeks gestation with single dose (SD) NVP given to the mothers plus two doses to the infants, in addition to zidovudine (ZDV) prophylaxis (from 28 weeks' gestation and for one week of ZDV in neonates) for the prevention of mother-to-child transmission of HIV-1.
Detailed Description
Multicenter, placebo-controlled, double blind, clinical trial where non immunocompromised women receiving the ZDV prophylaxis regimen from 28 weeks gestation, as recommended in Thailand, will be randomized to one of two arms:
Arm 1: NVP-NVP:
In women, one NVP 200 mg tablet at onset of labor+;
In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours+++
Arm 2: PL-NVP:
In women, one placebo tablet at onset of labor++;
In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours+++
Arm 3: LPV/r:
In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
women in Arm 1 will also receive 7-day ZDV 300mg bid plus 3TC 150mg bid from delivery. ++women in Arm 2 will also receive 7-day (ZDV+3TC) Placebo from delivery. +++If the new born weight less than 2500 g, nevirapine will be administered 2 mg./1 kg (As per Thai Guideline).
All infants will receive ZDV for at least one week. Follow-up of women and infants is carried out on an outpatient basis except for delivery and the first three days after delivery. Mothers and infants are followed-up for 24 months after delivery.
Note: The study was stopped and data unblinded upon DSMB recommendations in September 2010 because of changes in Thai PMTCT guidelines recommending use of HAART in all HIV infected pregnant women regardless of their CD4 count. At the time of unblinding 435 pregnant women had been enrolled and follow-up of these women and their children is continuing.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Pregnancy
Keywords
Thailand, Developing Countries, Prophylaxis, Mother-to-child transmission, HIV-1, HIV-1 infection, HIV Seronegativity
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
435 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
NVP-NVP:
In women, one NVP 200 mg tablet at onset of labor;
In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
Arm Title
2
Arm Type
Experimental
Arm Description
PL-NVP:
In women, one placebo tablet at onset of labor;
In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
Arm Title
3
Arm Type
Experimental
Arm Description
LPV/r:
In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
Intervention Type
Drug
Intervention Name(s)
Maternal and infant nevirapine
Intervention Description
In women, one NVP 200 mg tablet at onset of labor;
In neonates, NVP oral suspension 6 mg in the delivery room immediately
Intervention Type
Drug
Intervention Name(s)
Maternal placebo and infant nevirapine
Intervention Description
In women, one placebo tablet at onset of labor;
In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
Comparison between Arms 1 and 2 is double-blinded.
Intervention Type
Drug
Intervention Name(s)
Maternal lopinavir+ritonavir
Intervention Description
- In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
Intervention Type
Drug
Intervention Name(s)
zidovudine
Intervention Description
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
Primary Outcome Measure Information:
Title
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Time Frame
At birth, 7-10 days, 1, 2, 4 and 6 months of age
Secondary Outcome Measure Information:
Title
Safety for mothers and children of two NVP doses in neonates with and without maternal single dose NVP at onset of labor or LPV/r from 28 weeks gestation.
Time Frame
From randomization during pregnancy until 24 months after delivery
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Pre-Entry Criteria
Evidence of HIV infection (documented by two HIV antibody tests on two different dates)
Intend to be followed at a study site for the duration of the study
At least 18 years old
Written informed consent.
Inclusion Criteria:
Women are eligible for the study if they
met all pre-entry criteria
Evidence of HIV infection, as documented by two serology tests obtained at two different dates;
between 28 and 36 weeks gestational age;
antiretroviral naïve except for exposure to ZDV prophylaxis PMTCT;
CD4 count above 250 cells/mm3 (within 4 months prior to randomization)
agreement not to breastfeed;
consent to participate and to be followed for the duration of the study;
and the following laboratory values within 14 days prior to randomization:
hemoglobin > 8.5 mg/dl;
absolute neutrophil count > 750 cells/mm3;
platelets > 50,000 cells/mm3;
SGPT ≤ 5 times upper limit of normal;
serum creatinine ≤ 1.5 times upper limit of normal (women with a serum creatinine > 1.5 times upper limit of normal must have a measured eight-hour urine creatinine clearance > 70 ml/min).
Exclusion criteria:
Evidence of pre-existing fetal anomalies incompatible with life;
patients who meet the criteria of Classes III/IV of the WHO classification of HIV-associated clinical disease;
known hypersensitivity to any benzodiazepine;
active tuberculosis;
concurrent participation to any other clinical trial;
receipt of benzodiazepines or antiretroviral agent other than ZDV;
uncontrolled hypertension;
anticoagulant therapy or magnesium sulfate within 2 weeks of enrollment or the need for them during labor or at delivery.
If any of these conditions occurs after randomization, the women will be excluded from study drug dosing. Women with CD4 count lower than 250 cells/mm3 will be excluded from the study and offered HAART in the context of the national program.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Lallemant, MD
Organizational Affiliation
Institut de Recherche pour le Developpment
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nopparat Rajathanee Hospital
City
Kannayao
State/Province
Bangkok
ZIP/Postal Code
10230
Country
Thailand
Facility Name
Bhumibol Adulyadej Hospital
City
Saimai
State/Province
Bangkok
Country
Thailand
Facility Name
Chachoengsao Hospital
City
Muang
State/Province
Chachoengsao
ZIP/Postal Code
24000
Country
Thailand
Facility Name
Prapokklao Hospital
City
Muang
State/Province
Chantaburi
ZIP/Postal Code
22000
Country
Thailand
Facility Name
Nakornping Hospital
City
Mae Rim
State/Province
Chiang Mai
ZIP/Postal Code
50180
Country
Thailand
Facility Name
Sanpatong Hospital
City
Sanpatong
State/Province
Chiang Mai
Country
Thailand
Facility Name
Mae Chan Hospital
City
Mae Chan
State/Province
Chiang Rai
Country
Thailand
Facility Name
Mae Sai Hospital
City
Mae Sai
State/Province
Chiang Rai
Country
Thailand
Facility Name
Phan Hospital
City
Phan
State/Province
Chiang Rai
Country
Thailand
Facility Name
Chiang Saen Hospital
City
Chiang Saen
State/Province
Chiangrai
ZIP/Postal Code
57150
Country
Thailand
Facility Name
Chiangrai Prachanukroh Hospital
City
Muang
State/Province
Chiangrai
ZIP/Postal Code
57000
Country
Thailand
Facility Name
Wiangpapao Hospital
City
Wiangpapao
State/Province
Chiangrai
ZIP/Postal Code
57170
Country
Thailand
Facility Name
Banglamung Hospital
City
Banglamung
State/Province
Chonburi
ZIP/Postal Code
20150
Country
Thailand
Facility Name
Chonburi Hospital
City
Muang
State/Province
Chonburi
ZIP/Postal Code
20000
Country
Thailand
Facility Name
Panasnikom Hospital
City
Panasnikom
State/Province
Chonburi
ZIP/Postal Code
20140
Country
Thailand
Facility Name
Ao Udom Hospital
City
Sri Racha
State/Province
Chonburi
ZIP/Postal Code
20230
Country
Thailand
Facility Name
Kalasin Hospital
City
Muang
State/Province
Kalasin
ZIP/Postal Code
46000
Country
Thailand
Facility Name
Phaholpolphayuhasena Hospital
City
Munag
State/Province
Kanjanaburi
ZIP/Postal Code
71000
Country
Thailand
Facility Name
Khon Kaen Hospital
City
Muang
State/Province
Khon Kaen
Country
Thailand
Facility Name
Lampang Hospital
City
Muang, Lampang
State/Province
Lampang
ZIP/Postal Code
52000
Country
Thailand
Facility Name
Mahasarakam Hospital
City
Muang
State/Province
Mahasarakam
ZIP/Postal Code
44000
Country
Thailand
Facility Name
Maharaj Nakhon Si Thammarat Hospital
City
Muang
State/Province
Nakhon Si Thammarat
ZIP/Postal Code
80000
Country
Thailand
Facility Name
Nakhonpathom Hospital
City
Muang
State/Province
Nakhonpathom
Country
Thailand
Facility Name
Nong Khai Hospital
City
Muang
State/Province
Nong Kai
ZIP/Postal Code
43000
Country
Thailand
Facility Name
Pranangklao Hospital
City
Muang
State/Province
Nonthaburi
Country
Thailand
Facility Name
Pathumthani Hospital
City
Muang
State/Province
Pathumthani
ZIP/Postal Code
12000
Country
Thailand
Facility Name
Chiang Kham Hospital
City
Chiang Kham
State/Province
Phayao
ZIP/Postal Code
56110
Country
Thailand
Facility Name
Buddhachinaraj Hospital
City
Muang
State/Province
Pitsanulok
Country
Thailand
Facility Name
Rayong Hospital
City
Muang
State/Province
Rayong
ZIP/Postal Code
21000
Country
Thailand
Facility Name
Samutsakhon Hospital
City
Muang
State/Province
Samutsakhon
ZIP/Postal Code
74000
Country
Thailand
Facility Name
Songkhla Hospital
City
Muangsongkhla
State/Province
Songkhla
ZIP/Postal Code
90100
Country
Thailand
Facility Name
Hat Yai Hospital
City
Hat Yai
State/Province
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Trat Hospital
City
Muang
State/Province
Trat
ZIP/Postal Code
23000
Country
Thailand
Facility Name
Health Promotion Hospital Regional Center I
City
Bangkok
ZIP/Postal Code
10220
Country
Thailand
Facility Name
Health Promotion Center Region 10,
City
Chiang Mai
ZIP/Postal Code
50100
Country
Thailand
Facility Name
Fang Hospital
City
Chiang Mai
ZIP/Postal Code
50110
Country
Thailand
Facility Name
Chomthong Hospital
City
Chiang Mai
ZIP/Postal Code
50160
Country
Thailand
Facility Name
Somdej Pranangchao Sirikit Hospital
City
Chonburi
ZIP/Postal Code
20180
Country
Thailand
Facility Name
Regional Health Promotion Centre 6,
City
Khon Kaen
ZIP/Postal Code
40000
Country
Thailand
Facility Name
Lamphun Hospital
City
Lamphun
ZIP/Postal Code
51000
Country
Thailand
Facility Name
Phayao Provincial Hospital
City
Phayao
ZIP/Postal Code
56000
Country
Thailand
Facility Name
Vachira Phuket Hospital
City
Phuket
ZIP/Postal Code
83000
Country
Thailand
Facility Name
Samutprakarn Hospital
City
Samutprakarn
ZIP/Postal Code
10280
Country
Thailand
12. IPD Sharing Statement
Citations:
PubMed Identifier
15247338
Citation
Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-28. doi: 10.1056/NEJMoa033500. Epub 2004 Jul 9.
Results Reference
background
PubMed Identifier
15247339
Citation
Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M; Perinatal HIV Prevention Trial Group. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med. 2004 Jul 15;351(3):229-40. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
Results Reference
background
PubMed Identifier
16816557
Citation
Shapiro RL, Thior I, Gilbert PB, Lockman S, Wester C, Smeaton LM, Stevens L, Heymann SJ, Ndung'u T, Gaseitsiwe S, Novitsky V, Makhema J, Lagakos S, Essex M. Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana. AIDS. 2006 Jun 12;20(9):1281-8. doi: 10.1097/01.aids.0000232236.26630.35.
Results Reference
background
PubMed Identifier
20625263
Citation
Cressey TR, Jourdain G, Rawangban B, Varadisai S, Kongpanichkul R, Sabsanong P, Yuthavisuthi P, Chirayus S, Ngo-Giang-Huong N, Voramongkol N, Pattarakulwanich S, Lallemant M; PHPT-5 Team. Pharmacokinetics and virologic response of zidovudine/lopinavir/ritonavir initiated during the third trimester of pregnancy. AIDS. 2010 Sep 10;24(14):2193-200. doi: 10.1097/QAD.0b013e32833ce57d.
Results Reference
result
PubMed Identifier
26372485
Citation
Lallemant M, Le Coeur S, Sirirungsi W, Cressey TR, Ngo-Giang-Huong N, Traisathit P, Klinbuayaem V, Sabsanong P, Kanjanavikai P, Jourdain G, Mcintosh K, Koetsawang S; PHPT-5 study investigators. Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand. AIDS. 2015 Nov 28;29(18):2497-507. doi: 10.1097/QAD.0000000000000865.
Results Reference
result
PubMed Identifier
25992639
Citation
Sripan P, Le Coeur S, Amzal B, Ingsrisawang L, Traisathit P, Ngo-Giang-Huong N, McIntosh K, Cressey TR, Sangsawang S, Rawangban B, Kanjanavikai P, Treluyer JM, Jourdain G, Lallemant M, Urien S. Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV. PLoS One. 2015 May 19;10(5):e0126647. doi: 10.1371/journal.pone.0126647. eCollection 2015. Erratum In: PLoS One. 2015;10(6):e0130917. PLoS One. 2015;10(8):e0137368.
Results Reference
derived
Links:
URL
http://www.phpt.org
Description
Program for HIV Prevention and Treatment (Thailand)
Learn more about this trial
Maternal/Infant Peripartum NVP, Versus Infant Only Peripartum NVP, or Maternal LPV/r in Addition to Standard ZDV Prophylaxis for the Prevention of Perinatal (PMTCT) HIV in Thailand
We'll reach out to this number within 24 hrs